Cocaine abuse continues to be a pressing health and sociological problem confronting many developed nations. In America, thousands of new users are added each day and each year a large proportion die from overdose or other toxic influences. The effects on the unborn can be especially tragic. Significantly, abuse is detrimental not only to the well-being of the individual, but also effects others and degrades the infrastructure of society. The biochemistry of the action of cocaine is complex having perhaps the most unique and powerful reinforcing properties of any drug. While a number of pharmaceuticals have been evaluated, none have proven to be adequate. Hence, there remains no concrete medical solution to the cocaine problem and it has become obvious that alternative avenues must be explored. One such approach invokes immunological strategies for the direct treatment of cocaine abuse and addiction in preventative or rehabilitative contexts. In this way, social programs would be bolstered by an objective scientific foundation. We recently demonstrated the efficacy of an immunological strategy in rat behavioral paradigms using an anticocaine vaccine and a cocaine-binding monoclonal antibody (mAb). This proposal delineates the methodology necessary to 1) complete the current passive immunization aspect of our program by obtaining human and/or humanized anticocaine mAbs for eventual clinical application, and 2) implement catalytic anticocaine mAbs as an additional potent passive immunization protocol. With regard to the latter, we have preliminary data on catalytic mAbs that degrade cocaine and have new hapten designs and strategies for acquiring catalysts with the activity necessary to address cocaine addiction. Significantly, antibodies will be available from murine immunization and from combinatorial antibody libraries that would directly provide human mAbs. All mAbs would enter into our well-established rat models for the human condition. The work described herein provides the culmination in what will be a complete program for the immunopharmacotherapy of cocaine abuse.